Bespoke Biology

A common laboratory practice, growing microbes in specific conditions, has been performed for decades and it is at the heart of drug discovery, systems and synthetic biology, and the study of evolution on a molecular scale. But its own evolution has been left behind even throughout the boom of recent technological advances that have dramatically revolutionized biology. Current technology confines scientists and makes them place limitations on the scale or the design of a study.

Now, with the development of a do-it-yourself (DIY) framework named eVOLVER, Assistant Professor Ahmad ‘Mo’ Khalil (BME) is hoping to disrupt that longstanding experimental compromise. The work has been published online and is scheduled to appear as the cover story of the July issue of Nature Biotechnology.

The entire eVOLVER platform. Photo by Brandon Wong

Standard techniques for cell growth can be scaled up to grow large numbers of cultures at the same time, but culture conditions cannot be precisely controlled or customized. Technologies such as bioreactors allow for precise control over certain conditions, like temperature, but are very costly to parallelize and it is difficult to extend the technology beyond exactly what it was designed to do. eVOLVER is an automated platform, constructed cheaply and entirely in the lab, that can continuously monitor and control hundreds of individual cultures in real-time.

“Right now scientists build their experiments around the equipment that is available to them,” says Khalil. “We wanted to flip that concept on its head to allow scientists to customize their equipment based on the experiments they want to run.”

eVOLVER is also designed to connect to a network so that scientists can coordinate and run experiments over the internet. “I no longer have to be in the lab at odd hours if I am running an experiment,” says Brandon Wong, graduate student and co-inventor of eVOLVER. “I can monitor the progress and conditions in real-time on my phone and if I need to modify anything, I can do it from home instead of trekking into the lab.”

A smart sleeve (right) encapsulates a culture (shown without the sleeve on the left). Photo by Brandon Wong

To demonstrate its versatility, Khalil, along with Wong and collaborators, performed three distinctly different growth experiments with eVOLVER that would otherwise be very challenging for any other system. The first demonstrated how eVOLVER could be used to evolve cells in the laboratory in high throughput and over long periods of time under many different specific conditions. Second, they demonstrated that eVOLVER can be used to systematically test growth phenotypes of large cell libraries in fluctuating environments. The third and final set of experiments displayed the real-time versatility of eVOLVER by programming it to carry out complex fluid manipulations to mix and transfer media, experimental liquids or cultures, a capability that has not been available to current continuous culture systems.

eVOLVER was made possible with the development of technologies such as 3D printing and DIY software and hardware that did not all exist in such an accessible way just a few years ago. The device consists of three modules: the smart sleeve; a fluidic control module; and a modular hardware infrastructure. The smart sleeve is what monitors and controls the culture growth with printed circuit board sensors and actuators along with other electronic parts in an aluminum casing tube, attached to a 3D-printed mount. Circuit boards can be removed or added based on which experimental parameters are needed; a lab could program a fluctuating temperature control onto a board and only plug that into eVOLVER when the experiment needs that temperature control.

There are currently multiple beta-testers with their own eVOLVERs across the country and as the network grows, Khalil hopes that the many potential uses of eVOLVER will be showcased. “This could be a powerful platform to study the microbiome, or to evolve proteins in the laboratory in massively parallel fashion to generate new activities,” says Khalil. “It also supports our work in synthetic biology by allowing us to test and characterize synthetic genetic circuits in a more efficient and more experimentally robust way.” Creating a large network of users could lead to open-source protocols and data, which, in turn, can lead to increased reproducibility.

Laboratory equipment can be a financial burden on researchers and many are left with the choice of whether to buy one device over another—and sometimes the device a researcher needs doesn’t even exist. As a do-it-yourself, inexpensive and open-source platform, eVOLVER puts experimental design back into the hands of the scientists and their grant money back in their pockets.